Regulatory role for nucleosome assembly protein-1 in the proliferative and vasculogenic phenotype of pulmonary endothelium
Regulatory role for nucleosome assembly protein-1 in the proliferative and vasculogenic phenotype of pulmonary endothelium
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DOI：
10.1152/ajplung.00316.2007
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发表时间：
2008-03-01
影响因子：
4.9
通讯作者：
Stevens, Troy
中科院分区：
文献类型：
--
作者：
Clark, Jennifer;Alvarez, Diego F.;Stevens, Troy
肺微血管内皮细胞（PMVECs）富含祖细胞，这是其快速增殖和血管生成能力的基础。然而，这种增强生长潜力的分子基础尚不清楚。核小体组装蛋白1 （NAP1）及其相关蛋白家族在许多物种的细胞生长控制中起着重要作用。因此，我们试图确定NAP1是否有助于pmvec中观察到的快速增殖和血管生成。NAP1在两种快速生长的细胞类型中高水平表达，包括PMVECs和从PMVECs中选择的驻留微血管内皮祖细胞，而在缓慢生长的肺动脉内皮细胞（PAECs）中低水平表达。异源NAP1表达增加了PAECs的生长潜能，而抑制NAP1表达则降低了PMVECs的生长潜能。尽管NAP1对内皮细胞生长有影响，但它不影响内皮细胞选择性标记物（PECAM-1、VE-cadherin、von Willebrand因子）的表达，也不影响细胞类型特异性凝集素结合标准；PMVECs与格里菲斯草凝集素相互作用，而PAECs与螺旋果凝集素相互作用。pmvec具有比paec更高的基底跨电电阻，这表明它们具有更强的限制性势垒特性。NAP1表达的改变并没有使pmvec和paec之间的基础屏障功能正常化。为了研究NAP1的促生长作用是否影响血管形成，我们将内皮细胞混合到Matrigel中并皮下植入。在10天的时间里，PMVECs产生的血管比PAECs多8倍。异源NAP1在PAECs中的表达增加了这种细胞类型形成的血管的数量，其中血管的生长接近PMVECs。因此，我们的研究结果表明，NAP1是增殖和血管生成内皮细胞表型的重要调节剂，但不会对内皮细胞表型规范产生全局影响。
Pulmonary microvascular endothelial cells (PMVECs) are enriched with progenitor cells that underlie their rapid proliferation and vasculogenic capacity. However, the molecular basis for such an enhanced growth potential is unknown. Nucleosome assembly protein-1 (NAP1), and its related family of proteins, have been incriminated in control of cell growth in a range of species. We therefore sought to determine whether NAP1 contributes to the rapid proliferation and vasculogenesis that is observed in PMVECs. NAP1 was expressed at a high level in two fast-growing cell types, including PMVECs and resident microvascular endothelial progenitor cells that were selected from PMVECs, whereas it was expressed at a low level in slow-growing pulmonary artery endothelial cells (PAECs). Heterologous NAP1 expression increased the growth potential of PAECs, whereas inhibiting NAP1 expression reduced the growth potential of PMVECs. Despite its impact on endothelial cell growth, NAP1 did not influence the expression of endothelial cell-selective markers (PECAM-1, VE-cadherin, von Willebrand factor), and it did not influence cell type-specific lectin binding criterion; PMVECs interact with Griffonia simplicifolia lectin, whereas PAECs interact with Helix pomatia lectin. PMVECs possess a higher basal transelectrical resistance than do PAECs, indicative of their more restrictive barrier property. Changing NAP1 expression did not normalize this basal barrier function between PMVECs and PAECs. To examine whether the growth-promoting actions of NAP1 influence blood vessel formation, endothelial cells were mixed into Matrigel and subcutaneously implanted. PMVECs generated eightfold more blood vessels than did PAECs over a 10-day time course. Heterologous NAP1 expression in PAECs increased the number of blood vessels formed by this cell type, where blood vessel growth approached that seen with PMVECs. Thus, our findings indicate that NAP1 functions as an important regulator of the proliferative and vasculogenic endothelial cell phenotype without globally impacting endothelial cell phenotype specification.